PMID- 29052220
OWN - NLM
STAT- MEDLINE
DCOM- 20190409
LR  - 20211204
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Linking)
VI  - 103
IP  - 2
DP  - 2018 Feb
TI  - Efficacy From Strange Sources.
PG  - 253-261
LID - 10.1002/cpt.916 [doi]
AB  - Reverse translation (RT) refers to perceptions and observations of clinical 
      outcomes, both beneficial and harmful, that can lead to a hypothesis intended to 
      identify a new use of a drug that is different from the original use. I provide a 
      panoramic view of successes in RT from the historic discovery of penicillin to 
      the contemporary development of CAR (chimeric antigen receptor) T therapies. I 
      delineate the core principles of RT that shift discovery from serendipity to a 
      systematic strategy based on target identification and causal biology, 
      pharmacodynamic biomarkers that recapitulate disease pathophysiology, 
      confirmation of target engagement by clinical proof of concept studies, and 
      optimal selection of dose and interval. The article proposes four different 
      categories of RT and successful examples are provided for each category. It 
      concludes with a summary of open questions related to the business case of RT 
      that includes a comparison of the pros, cons, and barriers to future RT 
      development programs.
CI  - (c) 2017 American Society for Clinical Pharmacology and Therapeutics.
FAU - Lesko, Lawrence J
AU  - Lesko LJ
AD  - University of Florida at Lake Nona, Orlando, Florida, USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20171201
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
SB  - IM
MH  - Animals
MH  - Data Mining/*methods
MH  - Databases, Factual
MH  - Drug Development/*methods
MH  - Drug Discovery/*methods
MH  - Drug Interactions
MH  - Drug-Related Side Effects and Adverse Reactions/etiology
MH  - Evidence-Based Medicine/*methods
MH  - Humans
MH  - Models, Animal
MH  - Models, Theoretical
MH  - Molecular Targeted Therapy
MH  - Patient Safety
MH  - Risk Assessment
MH  - Translational Research, Biomedical/*methods
EDAT- 2017/10/21 06:00
MHDA- 2019/04/10 06:00
CRDT- 2017/10/21 06:00
PHST- 2017/09/05 00:00 [received]
PHST- 2017/10/13 00:00 [revised]
PHST- 2017/10/14 00:00 [accepted]
PHST- 2017/10/21 06:00 [pubmed]
PHST- 2019/04/10 06:00 [medline]
PHST- 2017/10/21 06:00 [entrez]
AID - 10.1002/cpt.916 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2018 Feb;103(2):253-261. doi: 10.1002/cpt.916. Epub 2017 Dec 
      1.